This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In this project, the role of cellular immune responses in maintaining nonpathogenic SIV infection in sooty mangabeys is being investigated in several ways. This study utilizes both SIV-infected and colony born SIV-negative sooty mangabeys housed at the Yerkes National Primate Research Center (YNPRC). Previously, we showed that naturally SIV-infected sooty mangabeys mounted a substantial Th1-type SIV-specific cellular immune response that was comparable in magnitude to SIV-infected rhesus macaques. In a subsequent study, the early host response to SIV in primary infection was compared in SIV-infected rhesus macaques and sooty mangabeys. While a robust SIV-specific cellular immune response was mounted in both species, rhesus macaques displayed greater and more prolonged non-virus-specific immune activation in acute infection compared to sooty mangabeys. Moreover, CD4+ T lymphocyte apoptosis and increased TNF-related apoptosis inducing ligand were only seen in macaques. This data points to the presence of species-specific differences in the early innate immune response and it appears that this could contribute to differential immune activation in natural and non-natural hosts of SIV infection.